We have identified a set of three proteins present on the surface of male and female gametes of malaria parasites which are the targets of anti-gamete malaria transmission blocking monoclonal antibodies (Mabs). Analogous proteins have been identified in two species of malaria parasite Plasmodium gallinaceum in chickens, and Plasmodium falciparum from in vitro culture in human red blood cells. The 3 target antigens of gametes of P. falciparum were of apparent m.w. of 255, 59 and 53 kilodaltons; the target antigens of P. galinaceum were of similar apparent m.w. All 3 porteins in P. falciparum are synthesized early in gametocyte development and before the formation of the gametes themselves. Both parasite species suppression of infectivity was mediated by two distinct Mabs each of which, however, precipitated all three proteins from the gametes or gametocytes. In P. falciparum the two suppressive Mabs recognized distinct epitopes on the gamete antigens one of which showed antigenic variation between different isolates. Following fertilization the zygotes begin to shed their previous surface antigens and two new surface proteins of 27 and 23 kilodaltons appear on the surface of zygotes transforming into ookinetes as shown in studies with P. gallinaceum. Using Mabs, the 23 K protein has been demonstrated to be a definitive target of post fertilization transmission blocking immunity.